Despite continually improving survival rates, growth outcomes for premature extremely low birth weight (ELBW) infants remain exceptionally poor. Growth failure is nearly universal in these infants as they near term gestation. High rates of protein loss and elevated energy expenditures uncompensated by adequate nutritional intake appear to be primary factors in producing this growth failure, perhaps producing metabolic changes that prioritize survival over growth. There is accumulating experimental, clinical, and epidemiologic evidence that abnormal fetal growth can result in adaptations which persist throughout the lifespan and increase the risk of disease. Growth restriction in ELBW infants occurs in the extrauterine environment during the last third of gestation, and although adaptive responses might be expected, they have not been examined. The goal of the present proposal is to test the overall hypothesis that nutritional inadequacies of the extrauterine environment induce adaptive responses in protein metabolism, energy expenditure, insulin sensitivity, and endothelial function in ELBW infants which persist throughout infancy. Studies will be performed in ELBW and normal control infants at term gestation, 4 and 18 months of age. The following specific aims will be pursued: 1) To assess protein kinetics and protein catabolism during enteral feeding and in response to increased protein intake in ELBW infants throughout infancy. Proteolysis, protein synthesis and protein catabolism will be measured using stable isotopic tracers of leucine, phenylalanine, and urea 2) To determine the rate of total energy expenditure, resting energy expenditure, and energy of activity in ELBW infants throughout infancy. Total energy expenditure, resting energy expenditure and the energy of activity will be assessed using the doubly labeled water method and respiratory calorimetry 3) To examine insulin sensitivity in ELBW infants throughout infancy. A glucose tolerance test will be performed and glucose oxidation measured. 4) To evaluate endothelial function in ELBW infants throughout infancy. Endothelial function will be by determining acetylcholine induced vasodilation using the laser doppler technique. These studies may form the basis for improved clinical and nutritional strategies for these infants, as well as a future opportunity to more thoroughly explore the potential mechanisms underlying these adaptations.